Background: The murine double minute 2 (MDM2), an oncogene, acts as a major regulator of the p53 protein. A polymorphism in the MDM2 promoter, SNP309 (T/G), has been shown to alter protein expression and may thus play a role in carcinogenesis. MDM2 is a nuclear phosphoprotein that binds to TP53 and inhibits TP53-dependent transcription. Aim of the work: This study aims to evaluate the association of the MDM2 promoter SNP309 and development of hepatocellular carcinoma among Egyptian patients with chronic viral hepatitis. Subjects and Methods: MDM2 SNP309 (T/G) genotyping was assayed in 67 HCC patients on top of HCV infection and 36 chronic viral hepatitis patients. MDM2 SNP309 genotyping was assayed using real time polymerase chain reaction (PCR). Results: The frequency of the distribution pattern of the MDM2 SNP309 TT, TG, and GG genotypes in HCC group were 38.8%, 50.7% and 10.4% respectively and that in the control group were 38.9%, 50% and 11.1% respectively. There was with no significant difference between the two studied groups with [p value 0.994]. There were no significant difference in the distribution pattern of the SNP309 (TT+TG versus GG or TG+GG versus TT genotypes between the studied two groups with P value 0.917 and 0.993 respectively. There was no significant difference between the MDM2 SNP309 genotypes and the type of viral infection whether it was HCV or HBV. There was no significant difference between the MDM2 SNP309 genotypes regarding the tumour site, size or number. The male:female ratio in HCC group was 4.2 and that in the control group was 1.4. AFP level was highly significantly increased in HCC group [40(7.6-164ng/dl)] than that of the control group [5(2.7-7.7ng/dl)] with P value of 0.001. In the control group, the distribution of the genotype (TT, GG and TG) and the presence of cirrhosis were (85.7%, 100% and 88.9%) with no significant difference [P value 0.725]. Conclusion: Current data suggest that the association between MDM2-SNP309 genotype and HCC in the cohort study in Egyptian population is not significant.